Pathogenesis and regulation mechanisms for Th1- and Th2-dependent allergic airway inflammation

Th1和Th2依赖性过敏性气道炎症的发病机制和调控机制

• 批准号: 18604001
• 负责人: NISHIMURA Takashi
• 金额: $ 2.5万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18604001/
• 关键词: Allergy-Asthma; Gene; Cell-Tissue; Animal; Immunology; アレルギー・ぜんそく; 気道アレルギー; Th2; CpG; サイトカイン; DNAアレイ; 免疫バランス; 乳酸菌; Th1

To overcome various immune diseases induced by disruption of type1/type2 immune balance, we have established Th1- or Th2-dependent immune diseases models. In the present project, we established allergic airway inflammation mouse models by adoptive transfer of antigen-specific Th1 or Th2 cells followed by the antigen inhalation and investigated precise cellular regulation and molecular mechanisms in the pathogenesis. In the present models, transfer of Th1 cells induced fatal airway hyperresponsiveness (AHR) associated with severe neutrophilia, whereas the cased of Th2 cells caused eosinophilia in the lung. Compared to the Th2-transferred model, mRNA expression levels of MUC5AC and Gob5, related to mucus hypersecretion in airway epithelium, were extremely lower in the Th1 -transferred model. Thus, it was demonstrated that the Th1-induced AHR was independent on such mucus hypersecretion, which was essential for elevation of AHR in Th2-mediated asthma. In the Th2-transferred model, we foun … More d that in vivo injection of TLR9 ligand, CpG remarkably suppressed the symptoms by blocking of Th2-cell migration into lung. To investigate the mechanism, we used IFN-γ knockout mice and neutralizing antibodies against type I cytokines such as IFN-α, β, and IL-12. As the results, IFN-α, β, and IL-12, but not IFN-γ, were required for the inhibitory effect of CpG on Th2-cell migration. These findings were highly valued for elucidation of the suppression mechanism mediated by down-regulation of Th2-cell migration into lung even at effector phase, suggesting that CpG would be expected as a tool for clinical application in Th2-dependent asthma.Furthermore, we evaluated inhibitory effects of lactic acid bacterium (LAB), which easily activate type1 immunity, on Th2-dependent asthma. As the results, it was suggested that oral intake of LAB may have preventative effects on the allergic inflammation at induction phase rather than therapeutic effects at effector phase. The present findings will contribute to elucidation of the pathogenesis and development of the proper regulation in allergic airway inflammation. Less

为了克服type1/type2免疫义平衡引起的各种免疫疾病，我们已经建立了Th1-或Th2依赖性免疫疾病模型。在本项目中，我们通过对抗原特异性TH1或Th2细胞的自适应转移，然后研究了抗原吸入，并研究了发病机理中的精确细胞调节和分子机制，从而建立了过敏性气道炎症小鼠模型。在目前的模型中，Th1细胞的转移诱导了与严重嗜中性粒细胞相关的致命气道高反应性（AHR），而Th2细胞的情况会导致肺中嗜酸性粒细胞。与Th2转移模型相比，在TH1转移模型中，MUC5AC和GOB5的mRNA表达水平与气道上皮中的粘液分泌相关。这就是证明Th1诱导的AHR对这种粘液分泌独立，这对于Th2介导的哮喘中AHR的升高至关重要。在Th2转移模型中，我们会……更多的是在体内注射TLR9配体，CpG通过阻止Th2细胞迁移到肺中，可以极大地抑制症状。为了研究该机制，我们使用了IFN-γ基因敲除小鼠，并对I型细胞因子（例如IFN-α，β和IL-12）中和抗体中和抗体。结果，IFN-α，β和IL-12，而不是IFN-γ，它们是CpG对Th2细胞迁移的抑制作用所必需的。这些发现高度重视，即使在效应阶段将Th2细胞迁移到肺中的下调介导的抑制机制也很高，这表明CpG可以作为依赖Th2依赖性哮喘的临床应用的工具。我们评估了乳酸细菌（易于激活）Thynogy thn22，我们评估了对乳酸细菌的抑制作用。结果是，建议在诱导阶段对过敏性注射有预防作用，而不是效应阶段的热效应。目前的发现将有助于阐明过敏气道注射中适当调控的发病机理和发展。较少的

项目成果

IL-17-producing gd T cells infiltrated into tumor site promote angiogenesis and tumor progression

浸润肿瘤部位的产生 IL-17 的 gd T 细胞促进血管生成和肿瘤进展

• 发表时间: 2007
• 作者: Daiko Wakita;et. al.
• 通讯作者: et. al.

NKT cells from IL-4-deficient mice are defective in early IFN-γ production in response to α-galactosylceramide

IL-4 缺陷小鼠的 NKT 细胞在响应 α-半乳糖神经酰胺的早期 IFN-γ 产生中存在缺陷

• 发表时间: 2007
• 期刊: Cancer Science 98
• 作者: Daisuke Noguchi;Yuji Togashi
• 通讯作者: Yuji Togashi

Generating tumor- or OK432-specific Th1 cells Applicable to clinical trial of Th1 cell therapy

产生肿瘤或OK432特异性Th1细胞 适用于Th1细胞疗法的临床试验

• 发表时间: 2007
• 作者: Takayuki Ohkuri;et. al.
• 通讯作者: et. al.

医学のあゆみ

医学史

• 发表时间: 2022
• 作者: 藤田陽子;野田岳志
• 通讯作者: 野田岳志

新規自己免疫性大腸炎モデルの確立:IL-6依存的spontaneous proliferationによるTc17エフェクター細胞の誘導

新型自身免疫性结肠炎模型的建立：IL-6依赖性自发增殖诱导Tc17效应细胞

• 发表时间: 2007
• 作者: Hidemitsu Kitamura;et. al.;北村 秀光;但馬 正樹
• 通讯作者: 但馬 正樹